Abstract Lung cancer mortality can be reduced by 20% via CT screening and treatment of early stage disease. Maximum health impact from screening will only be achieved if high-risk smokers undergoing lung screening receive assistance to stop smoking. While there are several known effective cessation interventions, many of these are not scalable within diverse community-based lung cancer screening programs or with smokers who are not seeking cessation treatment. Our goal is to develop a scalable and cost-effective cessation intervention for widespread implementation to yield the greatest benefits and the lowest costs to both individuals and society. Guided by the RE-AIM Framework, we are proposing a pragmatic telephone counseling RCT, designed at the intersection of scalability and intensity, for future implementation within the national tobacco quitline. Our experienced team will conduct a randomized trial of 1330 smokers who have registered for screening at 5 diverse screening sites, comparing: 1) usual care (UC): telephone counseling, in which smokers receive a standard protocol of up to 3 counseling sessions and free NRT, vs. 2) a multi-faceted, 8-session, intensive telephone counseling (ITC) protocol, tailored on screening result, with free NRT. Both arms receive brief advice to quit, with primary care engagement, both English and Spanish speakers are included, and tobacco treatment specialists will conduct the telephone counseling. The goal of the ITC arm is to leverage the increased motivation provided by the teachable moment of lung screening and to counteract the potential for reduced motivation to quit following a normal result. Further, two important aspects of our approach include a cost-effectiveness analysis and use of the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate the costs of the interventions relative to their impact on short- and long-term smoking-related outcomes. By including all smokers, regardless of readiness to quit, personalizing their tobacco-related health risks, and providing an evidence-based cessation intervention, we expect that the ITC arm will yield substantially higher quit rates with excellent potential for widespread implementation, resulting in a cost-effective intervention. The aims are: 1) To compare intensive telephone counseling (ITC) vs. usual care (UC) standard telephone counseling on biochemically verified 7-day, 30-day, and sustained abstinence. Intervention mediators and moderators will be assessed. 2) To evaluate reach and engagement of the interventions. 3) To conduct a cost-effectiveness analysis of ITC vs UC, in terms of cost per 3-, 6- and 12-month abstinence rates and quit attempts. The CISNET model will project the long-term impact of the interventions on cost per life year saved and quality-adjusted life years saved, lung cancer mortality reduction, and overall population mortality. This study will have a substantial public health impact by providing critical data to address scalability efforts by screening centers, insurers, and policy-makers.